Adv. Pharm NURS 8024 Week 1
2 Major Administration Routes - ANS-1. Enteral -most common, easy, cheap-BUT drug
absorption pathways can be complicated
2. Parenteral-IV, fast, more expensive, once in-cannot get back
\Absorption - ANS-entry of pharmacologic agent into plasma
\Active Transport - ANS-requires energy (ATP), Able to move drug from LOWER to HIGHER
concentration
\adipose tissue - ANS-can store drugs and hormones
\Bioavailability - ANS-Highest to Lowest
IV, IM, SC, PO, PR (Rectal), Inhalation, Transdermal
\Blood Brain Barrier (BBB) - ANS---physiological barrier between the circulatory system and
the central nervous system that establishes a privileged blood supply, restricting the flow of
substances into the CNS
--Drugs must pass through the CNS capillaries or be actively transported
-- Lipid soluble drugs penetrate the CNS by dissolving in the membrane of ENDOTHELIAL
CELLS
-- Ionized or polar drugs cannot pass due to the TIGHT KNIT CELLS WITHOUT SLIT
JUNCTIONS!
\Capillary Permeability and Drug Distribution - ANS-• Capillary permeability
• capillary structure & chemical nature of the drug
• Variance in capillary structure: slit junctions between
endothelial cells (liver and pancreas have this)
• Allows passage of plasma proteins... and thus, drug molecules
• Absent in the brain- "blood-brain barrier"
\Clinical Implications of Plasma Protein Binding - ANS-Drug displacement from albumin
substantial
source of drug interactions.....
• Class I drug - warfarin
• Highly protein bound - small fraction of free drug in plasma
↓
• Class II drug given - sulfa
• Displaces warfarin from albumin
• Rapid rise in free drug concentration
• Increased therapeutic effect- toxic effect
\Competition for Plasma Protein Binding: Class I (most drugs) - ANS-- Low dose/capacity
ratio
-Amount of drug < albumin binding capacity
-number of binding sites > available drug
\Competition for Plasma Protein Binding: Class II (minority of drugs) - ANS--High
dose/capacity ratio
-Amount of drug > albumin binding capacity
-High proportion of drug in "free" state = not protein bound
\Describe the 5 stages of CKD - ANS-Stage 1: Kidney Damage with NL GFR >90
Stage 2: Kidney Damage with mild decrease GFR 60-89
, Stage 3: Moderate decrease GFR 30-59
Stage 4: Severe decrease GFR 15-29
Stage 5: Kidney Failure GFR < 15 (or on dialysis)
Chronic Kidney Disease is either Kidney Damage or GFR < 60 for > 3 months
\Distribution - ANS-agent leaves the bloodstream and distributes to interstitial and
intracellular fluids
\Drug Absorption - ANS-Drugs are typically weak acids or weak bases
Role and size of MOLECULAR WEIGHT in drug absorption
\Drug Displacement and Vd - ANS---Dependent on Vd and therapeutic index of drug
--Large Vd verses small Vd (drug is less around)
\Drug Distribution--Blood Flow - ANS-Wide variance r/t unequal distribution of Cardiac
Output (CO)
- Highest in organs: heart, brain, lungs, kidneys, liver, gut
-Lower in skeletal muscle
_Still lower in adipose tissue
\Drug Metabolism -- Zero Order Kinetics (minority of drugs) - ANS-ASA, Ethanol, Phenytoin
Rate of metabolism is constant OVER TIME---therefore a CONSTANT AMOUNT of drug is
metabolized per unit of TIME
--HAS A STRAIGHT ELIMINATION LINE ON GRAPH
\Drug Metabolism-First Order Kinetics (most drugs) - ANS---Metabolic transformation of
drugs by enzymes
--Rate of drug metabolism is directly proportional to the concentration of free drug--so
CONSTANT FRACTION of drug per unit of time is eliminated
--Linear elimination pattern: reflected by 1/2 life of the drug
--Each half life cuts the drug concentration by 50%
At 2 Half lives= drug has been 75% removed
At 5 Half lives= drug is essentially removed from the body
--has a CURVED ELIMINATION LINE ON GRAPH
\Drug Molecular Weights - ANS-Most drugs weight from 100-1000
smaller sizes are easier to cross membranes
However, drugs can vary in size from MW of 7 (Lithium) to 50,000 (thrombolytic enzymes)
\Drug Reabsorbed at the Distal Tubule - ANS-This is when the drug is passively reabsorbed
( a lipid soluble un ionized drug); then Phase 1 and 2 metabolism, then drug is ionized or a
polar metabolite
\Drug Transport Methods: - ANS-Passive diffusion (no E needed)
Active transport (requires E)
Endocytosis
\Ellimination - ANS-Leaving the body-via urine, bile, feces, lungs, sweat, breast milk
\Endocytosis - ANS-Transport large molecules
Engulfment of drug molecule by cell membrane and transport into cell
\Enteral drug administration - ANS-oral, sublingual, rectal
drug absorption pathways complicated
**First-pass metabolism can limit the amount of drug that enters systemic circulation
influenced by food and other drugs
\Enzymes of drug metabolism are influence by - ANS-• Genetics
• Diet - proteins, carbs, flavonoids,
• Inducers - which
↑ enzyme synthesis
2 Major Administration Routes - ANS-1. Enteral -most common, easy, cheap-BUT drug
absorption pathways can be complicated
2. Parenteral-IV, fast, more expensive, once in-cannot get back
\Absorption - ANS-entry of pharmacologic agent into plasma
\Active Transport - ANS-requires energy (ATP), Able to move drug from LOWER to HIGHER
concentration
\adipose tissue - ANS-can store drugs and hormones
\Bioavailability - ANS-Highest to Lowest
IV, IM, SC, PO, PR (Rectal), Inhalation, Transdermal
\Blood Brain Barrier (BBB) - ANS---physiological barrier between the circulatory system and
the central nervous system that establishes a privileged blood supply, restricting the flow of
substances into the CNS
--Drugs must pass through the CNS capillaries or be actively transported
-- Lipid soluble drugs penetrate the CNS by dissolving in the membrane of ENDOTHELIAL
CELLS
-- Ionized or polar drugs cannot pass due to the TIGHT KNIT CELLS WITHOUT SLIT
JUNCTIONS!
\Capillary Permeability and Drug Distribution - ANS-• Capillary permeability
• capillary structure & chemical nature of the drug
• Variance in capillary structure: slit junctions between
endothelial cells (liver and pancreas have this)
• Allows passage of plasma proteins... and thus, drug molecules
• Absent in the brain- "blood-brain barrier"
\Clinical Implications of Plasma Protein Binding - ANS-Drug displacement from albumin
substantial
source of drug interactions.....
• Class I drug - warfarin
• Highly protein bound - small fraction of free drug in plasma
↓
• Class II drug given - sulfa
• Displaces warfarin from albumin
• Rapid rise in free drug concentration
• Increased therapeutic effect- toxic effect
\Competition for Plasma Protein Binding: Class I (most drugs) - ANS-- Low dose/capacity
ratio
-Amount of drug < albumin binding capacity
-number of binding sites > available drug
\Competition for Plasma Protein Binding: Class II (minority of drugs) - ANS--High
dose/capacity ratio
-Amount of drug > albumin binding capacity
-High proportion of drug in "free" state = not protein bound
\Describe the 5 stages of CKD - ANS-Stage 1: Kidney Damage with NL GFR >90
Stage 2: Kidney Damage with mild decrease GFR 60-89
, Stage 3: Moderate decrease GFR 30-59
Stage 4: Severe decrease GFR 15-29
Stage 5: Kidney Failure GFR < 15 (or on dialysis)
Chronic Kidney Disease is either Kidney Damage or GFR < 60 for > 3 months
\Distribution - ANS-agent leaves the bloodstream and distributes to interstitial and
intracellular fluids
\Drug Absorption - ANS-Drugs are typically weak acids or weak bases
Role and size of MOLECULAR WEIGHT in drug absorption
\Drug Displacement and Vd - ANS---Dependent on Vd and therapeutic index of drug
--Large Vd verses small Vd (drug is less around)
\Drug Distribution--Blood Flow - ANS-Wide variance r/t unequal distribution of Cardiac
Output (CO)
- Highest in organs: heart, brain, lungs, kidneys, liver, gut
-Lower in skeletal muscle
_Still lower in adipose tissue
\Drug Metabolism -- Zero Order Kinetics (minority of drugs) - ANS-ASA, Ethanol, Phenytoin
Rate of metabolism is constant OVER TIME---therefore a CONSTANT AMOUNT of drug is
metabolized per unit of TIME
--HAS A STRAIGHT ELIMINATION LINE ON GRAPH
\Drug Metabolism-First Order Kinetics (most drugs) - ANS---Metabolic transformation of
drugs by enzymes
--Rate of drug metabolism is directly proportional to the concentration of free drug--so
CONSTANT FRACTION of drug per unit of time is eliminated
--Linear elimination pattern: reflected by 1/2 life of the drug
--Each half life cuts the drug concentration by 50%
At 2 Half lives= drug has been 75% removed
At 5 Half lives= drug is essentially removed from the body
--has a CURVED ELIMINATION LINE ON GRAPH
\Drug Molecular Weights - ANS-Most drugs weight from 100-1000
smaller sizes are easier to cross membranes
However, drugs can vary in size from MW of 7 (Lithium) to 50,000 (thrombolytic enzymes)
\Drug Reabsorbed at the Distal Tubule - ANS-This is when the drug is passively reabsorbed
( a lipid soluble un ionized drug); then Phase 1 and 2 metabolism, then drug is ionized or a
polar metabolite
\Drug Transport Methods: - ANS-Passive diffusion (no E needed)
Active transport (requires E)
Endocytosis
\Ellimination - ANS-Leaving the body-via urine, bile, feces, lungs, sweat, breast milk
\Endocytosis - ANS-Transport large molecules
Engulfment of drug molecule by cell membrane and transport into cell
\Enteral drug administration - ANS-oral, sublingual, rectal
drug absorption pathways complicated
**First-pass metabolism can limit the amount of drug that enters systemic circulation
influenced by food and other drugs
\Enzymes of drug metabolism are influence by - ANS-• Genetics
• Diet - proteins, carbs, flavonoids,
• Inducers - which
↑ enzyme synthesis
